A Thin Form-Factor Interactive Surface Technology: Fill & Download for Free

With the usual disclaimer of "why would anyone care",I'll thank you for asking me,and use this as an opportunity to write where I think technology should (and perhaps is) going.I'll begin, if I may, with a short story: (Cue Flashback Harp music, fade out to 1999)When I was in my first year of college, one of the best lecturers I had, was Yosi Wiesel, a private sector IT expert,who taught the introduction to IT class,and who gave my class an analysis of where he thought technology was going.This is 16 years ago but I remember distinctively what he said, in what was one of our very first classes:"The devices we will use in the future will not be heavy computers,with huge disk space and more, larger programs and more elaborate, heavy, operating systems.Exactly the opposite.They will be small, limber, handheld devices.The programs will be replaced with applications, that we will consume as we need, when the majority of the SW will be online,and we will merely have the access UI on our small device,The data will not be "going" with us - it will be online,accessible from anywhere, anytime, when we need it.Now when I say "future" I mean a decade - Maximum".Most students attending?Laughed.They went on and on over the: "handheld surface won't be big enough","Internet speeds will never be fast enough",Some said "Microsoft won't allow it".everyone noted "Security Issues" and "wanting their data accessible"and basically the sentiment was: "This will never happen".Me?Granted, I had my doubts, especially about the time frame.But I was fascinated.I guess you couldn't blame the students - Remember:this is mid-late 1999.A few dozen kb/s internet connection is still common, forget "broadband", that's for VERY early adapters (and means 1MB),Our laptops have places for floppy disks, and we carry a few of those with us,Your phone is either a Motorola StarTec or a Nokia 6120.Microsoft was distributing the Windows Millennium Edition, "especially designed to withstand the "Y2K BUG"This was Microsoft's last DOS based OS, as well as a crime against humanity.When you said "cloud" people looked up to check for imminent rain."Wi-Fi? Is that a Chinese restaurant?"So that's that.The development of the iPhone would begin 5 years later.The first one would be sold 8 years later.Salesforce launched the first online CRM 3 years later.That company that opened up offices in California a year before?"Google" something? Was about to change the way we search for just about anything. And Amazon, a company that by then everyone already knew, would release the infrastructure and tools it used and introduce developers to widely available cloud infrastructure 7 years later, in the form of a company that wasn’t born yet - Amazon Web Services.The rest is history: Yosi was spot on.He was describing Smartphones, Mobile Apps, and Cloud Infrastructure, before they had names.End story.(Cue Flashback Harp music, fade back to 2015)The fact Yosi turned out to be right, stuck with me, and had a profound effect on me post graduation:My main mission with Israel's satellite TV, was driving content and viewing towards online viewing and towards mobile devices viewing;My startup revolved around SaaS;The Startup I later joined as VP Biz Dev was all about Cloud Infrastructure and Cloud migration;In the two Venture Capital funds I've worked for (still do, for the second one) my focus was and is SaaS, Internet and Mobile;I am now part of Startup Business Development team of the Amazon Web Services, the Global Cloud Computing platform leader.My view of technology, internet specifically, played a great part in my career and where I navigated it.So what technology/ies do I find indispensable?Wireless Broadband Internet Access.Wi-Fi/LTE/4G, it doesn't really matter which.The fact that we are nearing the stage of access anywhere is dramatic.Even more so - Our applications don't just take us there, they ARE there. Based on infrastructure like AWS, data bases, storage and even the compute servers are all in the cloud.A technological trend I'm very excited about is:Internet of Things (IoT)Our "things" now connect to the internet, "to us" and to other "things", allowing us to do and learn more, even about ourselves.I view this as an important trend that much like wireless access, will have a profound effect on our future.My teammates at Gemini Israel Ventures, share the same view, which is why we are the fund behind the Annual IoT Israel Summit.Here's the last one - IoT Israel Summit 2015(My Quora profile pic is from there...)At the end of this answer, I'll get back to these two technologies, how they converge, and what this may lead to.I enjoy the fact innovating is faster today.Open Source, Agile development, Communities, Sharing code, new versions on a weekly, daily basis (Sometimes even less...).So perception wise I lean towards Android.I love the open eco-sysetem, allowing me to download from wherever;I can customize my UI as I see fit,;I can switch to any device I want: I've had 4 Android phones by 3 different manufacturers;Innovation usually gets to my Android quicker.So, which technologies do I use now?No matter which device I use, my browser is Chrome.My Smartphone is an Android - Nexus 5.My house is connected to Amazon Echo and interacts with Alexa.My Tablet is a - 7″ Amazon Fire. (Sure, the kids have an iPad...)My HP Laptop runs on Windows 7......It's simply the laptop I got from work...This is the last Microsoft OS I will use.Especially after seeing the Windows 8 UI...Image by Noam Kaiser on TwitterIt's horrific.So my next laptop? Will be a Chromebook.I don't need a heavy OS, I need internet access.That's it.(Plus the guy who invented it is on Quora! Jeff Nelson!)My device choices reflect - I think so - my approach to technology.June 8th Update: Got the Samsung Chromebook - Love it.Which leads me to the final bit, my own prediction:In the not so far future, (more than a decade, but not a millennium either)the tablet, the smartphone, the laptop, the devices as we know them,will be history.From virtualization of environments, we will evolve into virtualization of devices.Our desktop, our interface units, our work surface,will all be projected and interactive.We will store nothing offline, and carry zero storage with us.The only thing we will carry will be a small wearable device,connected to the internet.​​(Yep, just like Nightwing (DC Comics)'s...)In fact...(The fantastic Cicret Bracelet)We're already well on our way there, and I’m proud to be a member of a company that is taking us there.This is far more than the "cool factor".As availability of connection becomes near complete, and devices get cheaper... that's right:We will be able to connect everyone.Especially those who couldn't connect so far.This will herald a chance for change.A good change.A chance for people deprived of access to knowledge and data.No more.(Not entirely unconnected to what this community tries to do here on Quora...)Granted - this could have negative effects on society and the young, sure.But technology, capability, is never bad.It can be misused.Plenty of work remains on that bit - we are ALREADY tackling it: Noam Kaiser's answer to What did you have as a child that kids today don’t have?But I'm excited about this prospect as a whole.I can hear it now..."But what about the camera?";"People would never give up their iPhone";"Networks will never be able to sustain this";"People won't click on thin air out of fear of looking ridiculous";"the resolution will never be good enough";"it won't work"...You know who that sounds like, to me anyway?The students who laughed at Yosi's lecture on what would become the smartphone.

Here the new innovations oil well drilling technology are given below and to know more visit this article.Drilling | New Technologies, InnovationsAdvances in technologies used for well drilling and completion have enabled the energy industry to reach new sources of oil and natural gas to meet rising demand around the world.New technologies have also helped reduce the environmental impact of energy production by allowing more oil and gas to be produced with fewer wells.Advances in technologies will play a critical role in meeting global energy demand because they enable the discovery of new resources, access to harsh or remote locations and the development of challenged reservoirs that previously were not economic to produce.Well completion is the final step of the drilling process, where the connection to hydrocarbon-bearing rock is established.Again, advances in technology have enabled more oil and natural gas to be recovered from the length of each well, improving production and reducing the environmental footprint of energy production.For example, by combining extended reach drilling capability with advanced stimulation technology, oil companies can optimize how and where stimulation fluid interacts with rock, allowing sustained production rates along the length of the wellbore.Companies are pushing completions in excess of 3,000 meters (9,842 feet) in length, compared to a typical completion of 30 meters a couple of decades ago.These types of drilling and completion technologies have also enabled the recent growth in production from shale and other unconventional oil and gas reservoirs in many parts of the world, using a combination of hydraulic fracturing and horizontal, extended reach drilling.Some examples of advancements in drilling technology are presented below:Horizontal DrillingHorizontal drilling is a directional drilling process aimed to target oil or gas reservoir intersecting it at the “entry point” with a near-horizontal inclination, and remaining within the reservoir until the desired bottom hole location is reached.While the construction of a directional well often costs much more than a conventional well, initial production is greater of a conventional well.Horizontal drilling provides more contact to a reservoir formation than a vertical well and allows more hydrocarbons to be produced from a given wellbore.For example, six to eight horizontal wells drilled from one location, or well pad, can access the same reservoir volume as 16 vertical wells.Using multi-well pads can significantly reduce the overall number of well pads, access roads, pipeline routes and production facilities, minimizing habitat disturbance, impacts to the public and the overall environmental footprint.Horizontal wells are usually drilled to enhance oil production and in some situations the improvement may be dramatic – enabling development of a reservoir which would otherwise have been considered uneconomic.There are many kinds of reservoir where the potential benefits of horizontal drilling are evident:in conventional reservoirs Thin reservoirs; Reservoirs with natural vertical fractures; Reservoirs where water (and gas) coning will develop; thin layered reservoirs; heterogeneous reservoirs;in unconventional reservoirs shale gas/oil, tight gas/oil, CBM, heavy oil, oil sands, etcThe initial vertical portion of a horizontal well is typically drilled using the same rotary drilling technique that is used to drill most vertical wells, wherein the entire drill string is rotated at the surface (the drilling of vertical sections is also possible by the use of downhole motor just above the bit, like the VertiTrak or TruTrak, where only the bit rotate while the drilling string remains firm).From the kickoff point to the entry point the curved section of a horizontal well is drilled using a hydraulic motor mounted directly above the bit and powered by the drilling fluid.Steering of the hole is accomplished through the employment of a slightly bent or “steerable” downhole motor (today the technology of directional drilling has improved by the use of the “RSS: Rotary Steerable System” that permit to steer an hole continuing the rotation of the drilling string. The RSS increase the safety and the drilling efficiency).Downhole instrument packages that transmit various sensor readings to operators at the surface are included in the drill string near the bit.Sensors provide the azimuth (direction versus north) and inclination (angle relative to vertical) of the drilling assembly and the position (x, y, and z coordinates) of the drill bit at all times.Additional downhole sensors can be, and often are, included in the drill string, providing information on the downhole environment (bottom hole temperature and pressure, weight on the bit, bit rotation speed, and rotational torque).They may also provide any of several measures of physical characteristics of the surrounding rock such as natural radioactivity and electrical resistance, similar to those obtained by conventional wire line well logging methods, but in this case obtained in real time while drilling ahead.The information is transmitted to the surface via small fluctuations in the pressure of the drilling fluid inside the drill pipe.Horizontal Drilling Technology (from Schlumberger)Application of horizontal drilling technology for unconventional gas exploitation (from American Energy Innovation)Multilateral DrillingSometimes oil and natural gas reserves are located in separate layers underground and multilateral drilling allows producers to branch out from the main well to tap reserves at different depths.This increases production from a single well and reduces the number of wells drilled on the surface.A multilateral well is a single well with one or more wellbore branches radiating from the main borehole.It may be an exploration well, an infill development well or a reentry into an existing well.It may be as simple as a vertical wellbore with one sidetrack or as complex as a horizontal, extended-reach well with multiple lateral and sublateral branches.General multi- lateral configurations include:multibranched wells, forked wells, wells with several laterals branching from one horizontal main wellbore, wells with several laterals branching from one vertical main wellbore, wells with stacked laterals, and wells with dual-opposing laterals.Multilateral Well Configurations (from Schlumberger)These wells generally represent two basic types:vertically staggered laterals and horizontally spread laterals in fan, spine-and-rib or dual-opposing T shapes.A successful multilateral well that replaces several vertical wellbores can reduce overall drilling and completion costs, increase production and provide more efficient drainage of a reservoir. Furthermore, multilaterals can make reservoir management more efficient and help increase recoverable reserves.Regardless of the level of complexity, multi- lateral wells today are drilled with state-of-the art directional drilling technology, but there is always a certain risks ranging from borehole instability, stuck pipe and problems with overpressured zones to casing, cementing and branching problems.Advantages of multilateral systems increasingly outweigh the disadvantages.Multilateral well configurationsMultilateral wells configuration enhance productivity.In shallow or depleted reservoirs, branched horizontal wellbores are often most efficient, whereas in layered reservoirs, vertically stacked drainholes are usually best.In fractured reservoirs, dual-opposing laterals may provide maximum reservoir exposure, particularly when fracture orientation is known (From Schlumberger Oilfield review)Extended Reach DrillingAn extended-reach well is one in which the ratio of the measured depth (MD) vs. the true vertical depth (TVD) is at least 2:1.Extended-reach wells are expensive and technically challenging, however, they can add value to drilling operations by making it possible to reduce costly subsea equipment and pipelines, by using satellite field development, by developing near-shore fields from onshore, and by reducing the environmental impact by developing fields from pads.Extended Reach Drilling allows producers to reach deposits that are great distances away from the drilling rig and this help producers tap oil and natural gas deposits under surface areas where a vertical well cannot be drilled, such as under developed or environmentally sensitive areas.Today, as the Horizontal Drilling, also the Extend Reach Drilling use the technology of the “RSS: Rotary Steerable System” that permit to steer an hole continuing the rotation of the drilling string with an improvement of the safety and the drilling efficiency.Moreover, the selection of a drilling fluid must balance a number of critical factors.The fluid must providea stable wellbore for drilling long open- hole intervals at high angles, maximize lubricity to reduce torque and drag, develop proper rheology for effective cuttings transport, minimize the potential for problems such as differential sticking and lost circulation, minimize formation damage of productive intervals.Pipe rotation is another critical factor in hole cleaning.The objective of the hole- cleaning program in ERW is to improve drilling performance by avoiding stuck pipe, avoiding tight hole on connections and trips, maximizing the footage drilled between wiper trips, eliminating backreaming trips prior to reaching the casing point and maximizing daily drilling progress.Example of ERW from TotalExample of ERW from SchlumbergerAutomated drillingAutomated drilling is one of the oil industry’s most important innovation targets.The sources now being tapped, such as shale gas and coal-bed methane, require a very large number of wells, and automating the drilling process would be an obvious way to keep the costs under control, and also gets around a problem which many sectors of engineering are experiencingAutomated drilling would be faster, more efficient, and safer, as it reduces the number of workers on site.Through sensors mounted on the drillbit, the system monitors the trajectory of the drill and its performance as it travels through the site geology, and controls its path to ensure that it meets the top hole precisely.Automating drilling takes in three stages of autonomy:The first is to mechanise the drilling equipment, such as the machinery which connects lengths of drill pipe.The second is to monitor torque and weight on the drill bit, and control these parameters to achieve optimum rate of penetration and the route of the bore-hole.The third level is to automate the entire process, including the speed of the pumps controlling drilling mud.The SCADAdrill computer system connects to the existing instruments and controls of a drilling rig.It can thus operate the rig machinery and monitor all aspects of the drilling process.In fact, the monitored parameters serve as the feedback control for the rig machines. In this way the orientation of the borehole is constantly checked as it is being drilled, helping to ensure that the well is drilled efficiently and that it reaches its target.Currently, wells are drilled using a stage by stage process:The initial bore is drilled down until the sides start to become unstable; any further down and they would start to collapse.At this point, the drill is stopped, the bore is lined with steel pipe, and the gap between the side of the bore and the outside of the pipe filled with grouting.The next stage of the bore has to be inside this hole, so a smaller diameter drill bit is used;the drilling again continues until the hole is on the verge of collapsing, then it is lined, and the process continues, with the diameter of the bores reducing each time.Shell is developing an expandable casing, which would allow the end of each tube to be ‘flared out’ to that it fits over the end of the tube below it.This can be done using a grade of steel which stretches while still remaining within the strengh parameters needed to stabilise the bore, or by using a slotted tube — a pattern of slots are scored into the surface of the outside and inside of the tube, not penetrating the full thickness of the steel, but allowing the end of the tube to expand by stretching the thinner sections of steel left by the slots.This technique would have a number of advantages:First, it reduces the amount of energy needed to drill the bore; wider bores need more energy because they have to displace more material, so for a given depth of bore, less rock has to be removed.It also uses less steel, less cement grouting, and less drilling mud; as well as a smaller drilling rig.It also allows greater depths to be achieved.

Photonic crystals: emerging biosensors and their promise for point-of-care applicationsHakan Inan, Muhammet Poyraz, [...], and Utkan DemirciAdditional article informationAbstractBiosensors are extensively employed for diagnosing a broad array of diseases and disorders in clinical settings worldwide. The implementation of biosensors at the point-of-care (POC), such as at primary clinics or the bedside, faces impediments because they may require highly trained personnel, have long assay times, large sizes, and high instrumental cost. Thus, there exists a need to develop inexpensive, reliable, user-friendly, and compact biosensing systems at the POC. Biosensors incorporated with photonic crystal (PC) structures hold promise to address many of the aforementioned challenges facing the development of new POC diagnostics. Currently, PC-based biosensors have been employed for detecting a variety of biotargets, such as cells, pathogens, proteins, antibodies, and nucleic acids, with high efficiency and selectivity. In this review, we provide a broad overview of PCs by explaining their structures, fabrication techniques, and sensing principles. Furthermore, we discuss recent applications of PC-based biosensors incorporated with emerging technologies, including telemedicine, flexible and wearable sensing, smart materials and metamaterials. Finally, we discuss current challenges associated with existing biosensors, and provide an outlook for PC-based biosensors and their promise at the POC.1. IntroductionBiosensing is an emerging analytical field for the detection of biochemical interactions leveraging electrical, optical, calorimetric, and electrochemical transducing systems.1,2These transduction mechanisms are employed to translate changes and variations within the biological domain into a readable and quantifiable signal (e.g., association, dissociation, and oxidation).3Biosensors are most notably employed for detecting various biological targets, such as cells,4bacteria,5,6viruses,7proteins,8hormones,9enzymes,10and nucleic acids,11to facilitate the diagnosis and prognosis of diseases. Currently, state of the art clinical laboratories require trained personnel to perform sample collection, testing, and analysis using sophisticated biosensing devices in centralized clinical settings (Fig. 1). Staffing the necessary personnel to ensure accurate and reliable readings can be costly, and results are subject to operator error.12,13Although certain automated instrumentation has been used to simultaneously process multiple patient samples at large volumes (e.g., hematology analyzers), technicians are still needed for device oversight and maintenance.14,15Centralized laboratories also perform immunoassays and nucleic amplification strategies, but these methods are time consuming, labor intensive, and expensive. As an example, enzyme-linked immunosorbent assay (ELISA) requires several experimental steps, including antibody immobilization, target binding, labeling, substrate incubation, signal production, and multiple washing steps.16,17Fig. 1Current challenges of biosensing tests for the POC applications. Biosensors face critical impediments at the POC due to large sample volume, transfer of samples to a central site, and being bulky and expensive. These challenges are most obvious at remote ...Recently, substantial research efforts have been devoted to the development of in vitrodiagnostic tests including point-of-care (POC) devices with the market volume estimated to reach US$ 75.1 billion by 2020.18One of the main drivers for these POC technologies is the detection of diseases in resource-limited countries.19–25For example, commercial POC kits have been recently developed to detect human immunodeficiency virus (HIV) and tuberculosis in such settings.26However, there are significant logistical, technical, and social barriers that need to be overcome when performing testing at these sites, and many of these technologies still require the recruitment and training of personnel (Fig. 1).14,27–29,30Thus, there exists a need to develop affordable, sensitive, rapid, portable, label-free, and user-friendly POC diagnostic tools.31–33Incorporation of microfluidics and nanotechnology into biosensing platforms holds great promise to address the aforementioned challenges. Sensitive technologies, such as localized and surface plasmon resonance, electrical sensors, interferometric biosensors, and photonic crystal (PC)-based bio-sensors, have been employed as diagnostic devices (Table 1).34–40PC-based biosensors hold many advantages over other existing competing biosensing technologies, including cost-effective fabrication and short assay time (Table 2). PC structures have been used to detect a wide array of biotargets in biological sample matrices, such as blood, urine, sweat, and tears,41–43and can be fabricated using various inexpensive fabrication methods, such as colloidal self-assembly, hydrogels, and mold-based replica imprinting.44–46Table 1General overview of PC-based biosensorsTable 2Comparison of PC-based biosensors with selected competing technologiesIn this review, recent incorporation of PC structures within emerging label-free biosensing platforms is discussed, including their applications for detecting proteins, nucleic acids, allergens, pathogens, and cancer biomarkers.47–50We will also provide a broad overview of PC structures and PC-based biosensors and their potential utilization as POC diagnostic tools. We describe various aspects of PC-based biosensors, including (i) PC structures and fabrication techniques, (ii) principles of PC-based biosensing, (iii) emerging technologies incorporating PC-based biosensors for potential POC applications, (iv) multi-target detection capability for PC-based biosensors, (v) surface chemistry approaches, (vi) current challenges and limitations for biosensors at the POC, and (vii) future outlook for PC-based biosensors at POC diagnostics.2. Photonic crystal structures and fabrication techniquesPC structures consist of spatially arranged periodic dielectric materials that uniquely interact with light, providing high efficiency reflection at specific wavelengths. There are many examples of PC-type periodically nanostructured surfaces observed in nature.51For instance, the bright iridescent color of the Morpho rhetenor butterfly,52peacock,53Eupholus magnificus insect,54sea mouse55and opals56are all associated with the geometrical arrangement on their surface, where broadband light illuminates and reflects through PC structures (Fig. 2).52In practice, PC structures can be fabricated in one-dimensional (1-D), two-dimensional (2-D) or three-dimensional (3-D) orientations incorporating microcavities,57waveguides,58slabs,59multi-layered thin films,60and porous geometries61(Fig. 3). A diverse range of materials, such as silicon (Si),62glass,63polymers,64colloids,65–68and silk,69–71are used in the fabrication of PC structures (Table 1).Fig. 2PC structures commonly found in the nature. Bright iridescent color of these objects is due to the presence of geometrical periodic elements in their structures. Shown are four types of PC structures: 1. (a and b): 1-D (Morpho rhetenor butterfly), 2. ...Fig. 3Types of photonic crystals. (a) 1-D slab is one of the most exploited PC structures for biosensing applications. Refractive index alternates in one dimension only (in x, or in yaxis) by forming air gaps in between substrate structures.227It also possess ...PC structures are fabricated using various methods, including self-assembly and lithography techniques. For instance, colloids composed of hydrogel polymers,72silica,73or polystyrene74are transferred from solution and self-assembled (viasedimentation, spin coating, or vertical deposition44,75) onto a surface to create PC structures that reflect iridescent color.75–77In addition, hydrogels are utilized in combination with colloidal particles in the fabrication of PC structures. While these self-assembly methods are inexpensive, precisely controlling the dimensions and geometry of the underlying PC structure is difficult. Top-down approaches, including electron beam lithography (e-beam), nanoimprint lithography (NIL), electrochemical etching, and thin film deposition techniques,78,79are alternatives to bottom-up self-assembly methods. Briefly, in the e-beam process, an electron beam is used to write a desired pattern onto a substrate (often silicon), which is previously coated with an electron-sensitive resist. The resist is then developed, and the electron-beam pattern is transferred to the substrate via etching. Performing this method requires e-beam lithography devices, which are large, expensive and require skilled operators. NIL is a rapid, simple, and scalable pattern transfer technique alternative to e-beam lithography.80In NIL, a pattern is initially produced using deep UV/e-beam lithography on a master mold, which can be easily transferred to daughter replicas. The NIL method has been used to mass-produce PC structures rapidly and reliably; however, only a finite number of replicas can be generated from a single mold due to wear.79Electrochemical etching can be used to fabricate porous Si structures that produce a photonic band gap due to formed periodic trenches. Electrochemical etching of Si is inexpensive and can be performed in research labs. Although trenches and channels provide a higher surface area for chemical interactions, large biomolecules may cause aggregation and blocking of the channels (e.g., cells) when using clinical samples.Overall, a wide range of materials and fabrication methods is available for the development of PC structures. Using PC structures for POC applications is highly feasible due to the availability of inexpensive fabrication materials such as hydro-gels and colloidal particles and the scalable production method using NIL. The theoretical background behind the PC phenomenon and how these PC structures are used as biosensors are discussed in the following section.3. Principles of PC-based biosensingA periodic arrangement of dielectric materials creates a photonic band gap when a range of electromagnetic waves cannot propagate due to the destructive interference of incident light with reflections at dielectric boundaries.81PC structures can be produced from a variety of geometries, including Bragg reflectors, slabs, opals, microcavities, and colloids. An optical phenomenon describing most of these structures can be deduced from understanding a simple Bragg structure. A typical Bragg reflector consists of alternating high and low refractive index dielectric thin film layers (Fig. 4a). The optical thicknesses of these layers are designed to be one quarter of the wavelength of incident light (λ) (eqn (1)). Multiple reflections from consecutive layers provide constructive interference and result in total reflection (Fig. 4b). Light at this reflected wavelength resides in a photonic band gap region (Fig. 4c), and cannot propagate at normal incidence.82Fig. 4The design and optical response of simple PCs. (a) A Bragg reflector consisting of alternating low and high refractive index of dielectric layers. At specific wavelengths, reflections from consecutive layers constructively interfere with each other and ...(1)Another common PC structure is comprised of periodically modulated thin films, which are known as 1-D slabs. 1D-PC structures are commonly fabricated from a high refractive index coating layer over a periodically arranged low refractive index grating layer (Fig. 4d). In these PC gratings, only the zeroth order mode is allowed, while higher order modes are restricted at normal incidence, provided that the period of the grating (Λ) is smaller than the wavelength of the incident light (Λ < λ). Gratings of this type are also called subwavelength gratings, and exhibit efficient optical resonances.83Subwavelength PC gratings can be designed to reflect a narrow band of wavelengths and produce a sharp peak in the reflection spectrum (Fig. 4e).84,85Resonance occurs when a diffracted mode from the grating couples to a leaky waveguide mode. Radiation from the leaky mode constructively interferes with the reflected wave and destructively interferes with the transmitted wave, resulting in a resonant reflection.83The resonance wavelength peak is determined by the period (Λ) of PC gratings and the effective refractive index (neff) under resonance conditions (eqn (2)).86λresonance= neffΛ(2)This resonance behavior of PC gratings is highly sensitive to the localized changes in dielectric permittivity on the crystal surface, which makes it suitable for sensing applications. In this regard, PC structures are widely utilized to develop sensing platforms for multiple applications of chemical sensing, environmental sensing, and more specifically, biosensing.87–90Briefly, a biochemical interaction (e.g., binding) on the PC surface causes a change in the effective refractive index, which results in a shift of the resonance wavelength peak, which is proportional to the concentration of the biotarget (Fig. 5). PC structures have gained significant attention as sensitive transducers and have been incorporated into biosensors that capture, detect, and quantify various biological molecules, such as pathogens,7,47,91–96DNA,97–101proteins, enzymes,102,103glucose,42,104–106cells,107,108toxins,109and allergens.110Fig. 5Overall mechanism of biosensing using photonic crystals. (a) An example of the 1-D PC slab surface. (b) Corresponding resonance peak wavelength for this PC slab. (c) Functionalization of the slab surface and biological binding event via antigen–antibody ...4. Emerging technologies incorporating PC-based biosensors for potential POC applicationsRecent advances in microfluidics, telemedicine, flexible materials, and wearable sensing technologies hold promise to provide compact and portable platforms in biosensing applications at POC for the rapid, reliable, accurate, on-site, and label-free detection of biotargets.111–1184.1 MicrofluidicsMicrofluidics technology offers considerable benefits to bio-sensing systems, particularly the POC devices. These advantages include (i) inexpensive fabrication materials (e.g., glass, paper and polymers), (ii) ability to control low sample volume, (iii) ease of integration with optical platforms, and (iv) flexibility in producing multiple channels to allow multiplexed testing platforms.119–121PCs-integrated with microfluidic technologies are emerging as powerful biosensing diagnostic tools with the integration of these features.50,122For instance, integration of 1-D PC slabs within a microfluidic channel network at the bottom of a 96-well plate was used to detect immunoglobulin gamma (IgG).46This microfluidic-integrated platform enabled the concurrent multiplex detection of molecules using only 20 μL of the sample (Fig. 6). In another study using a colloidal polystyrene-based PC structure integrated with microfluidics, IgG molecules were captured and detected down to mg mL−1levels.123PC structures have also been incorporated with polymer microfluidic channels to detect proteins; for example, a slotted PC cavity fabricated from Si was shown to detect 15 nM of avidin protein.124,125Fig. 6PC biosensors integrated with microfluidic platforms for POC applications. (a) Multi-well plate integrated with a network of microfluidic channels with PC-based biosensors at the bottom. Reproduced from ref. 46 with permission from The Royal Society of ...4.2 TelemedicineSmartphones have been increasingly utilized in medical diagnostics and healthcare applications, such as cell counting from whole blood, immunoassay testing, and imaging.111,126,127Smartphones will likely play an important role in the development of new biosensing platforms due to their wide availability, portability, compactness, capacity for data processing, ease of integration with microfluidic devices, and high-resolution optical components.111,128Recently, camera and optical systems in cell-phones have been integrated with microfluidic, microscopy, and photonic crystal technologies for the spectral analyses of bio-sensing applications.126,129–134For instance, a 1-D PC slab was integrated with a smartphone to measure IgG concentration. The phone camera was used as a spectrometer to measure the transmission spectrum from the PC structures.135Although the system produced a reliable dose–response curve, adsorption of biomolecules could only be measured under dry conditions. Thus, further study with aqueous samples is required before this platform could be used to directly analyze clinical samples at the POC. In another study, a 1-D PC slab was integrated with a complementary metal–oxide–semiconductor (CMOS)-based smartphone camera to detect anti-recombinant human protein CD40 (Cluster of Differentiation-40), streptavidin, and anti-EGF antibody (Fig. 7).136Fig. 7PC structure integrated with a smartphone for biosensing applications at the POC. (a) Drawing representing a general scheme of a PC incorporated smartphone. The CCD camera of the phone was utilized as an optical sensing element. (b) Actual image of the ...Smartphone-integrated platforms hold promise to address portability related issues at the POC, though their direct use in clinical applications is challenging because complex specimens, such as blood and tissue, need to be preprocessed before being brought into contact with the device.4.3 Wearable and flexible sensorsWearable sensors and flexible materials have recently gained attention for continuous and real-time monitoring of the physiological parameters and general health status of individuals.137–142For instance, they have been employed to measure the heart rate, skin temperature, blood oxygen levels, and more recently glucose sensing from sweat.143–145Wearable sensors are currently worn as wristbands, skin patches, and fabric patches. From a fabrication perspective, various nanotechnology-based techniques and materials are used for the production of these flexible and wearable sensors. In a recent study, a PC structure was designed with 2-D holes (with a diameter of ~100 nm) to evaluate strain changes.146This flexible sensor could be bent without losing its optical properties (Fig. 8a and b), and provided a sensitivity that was independent of deformation. In another study, colloidal polystyrene spheres were deposited on a flexible polyimide film.147A strain applied over this flexible film resulted in a blue shift in the reflection maxima (Fig. 8c and d).Fig. 8Flexible and wearable PCs in sensing applications. (a) Picture of the Si membrane integrated with a photonic crystal. (b) 2-D holes with a waveguide to couple light into a flexible photonic crystal structure. Reproduced from ref. 146, copyright (2014) ...3-D PC structures have also been incorporated into wearable sensors. For example, 3-D PC structures were investigated under pressure and may conceptually be used for detecting the severity of blast exposure to evaluate traumatic brain injury of soldiers in the battlefield.148,149In this study, 3-D voids were fabricated in an SU-8 resist to create 3-D PC structures that exhibited a color in the visible spectrum. These structures were exposed to varying high pressures (410 to 1090 kPa) to measure blast strength (Fig. 8e), and it was determined that large external forces could be detected by visual inspection (Fig. 8f–h). The PC structure that was exposed to high external forces underwent structural deformation, resulting in a color change. This change was used to estimate the degree of pressure on the PC structure. While this work is promising, using these detectors on soldiers’ uniforms is conceptual and their implementation in this field has not yet been evaluated.4.4 Smart materialsSmart materials are an emerging class of responsive substances that can modify their physical or chemical properties, mostly reversibly, against external stimuli such as pH, temperature, electrical field, and light.150,151Smart materials, such as hydrogels, polyionic liquids, graphene, and carbon nanotubes (CNTs), have been used for various applications, including biosensing. In particular, their incorporation into PC structures holds promise for rapid, sensitive, and reliable biosensing. Hydrogel materials are 3-D nanostructured polymers consisting mostly of water. Hydrogels may be responsive to external stimuli, such as temperature, pH, or bio-stimuli such as antigen–antibody interactions.45,72,152–155For instance, PC structures comprised of hydrogel materials can be used as biosensors for the detection of DNA, proteins, antibodies and enzymes by monitoring the changes in lattice spacing or refractive indices.41,43,156–159In this respect, hydrogel-based PC structures provide either quantitative spectral results or qualitative naked-eye detection of biotarget concentrations.41Hydrogel-based PC structures hold great promise for POC applications owing to their cost-effective fabrication and simple optical detection systems. In a recent study, a hydrogel-based nanoporous PC structure was employed for label-free detection of rotavirus with concentrations ranging from 6.35 μg mL−1to 1.27 mg mL−1(Fig. 9a and b).160Polyionic liquids (PILs) are a class of polymeric materials containing repeating ionic monomeric units, which have recently been demonstrated for sensing applications.161,162In one such study, PIL was used to fabricate a 3-D macroporous PC structure, that exhibited Bragg reflection in the visible wavelength range, to detect a variety of ions.163Fig. 9Smart material- and metamaterial-based PCs for sensing. (a) Hydrogel-based PCs for the detection of rotavirus. (b) SEM image of the hydrogel structure. (a and b are reproduced from ref. 160 with permission from The Royal Society of Chemistry) (c) 3-D ...Hydrogels can also be used in combination with other materials including graphene or carbon nanotubes (CNTs) to produce PC structures. In one such study, graphene oxide was deposited on a silicon wafer and embedded into a hydrogel matrix to detect beta-glucan.164Graphene based-PC structures have also been investigated for enhanced sensitivity biosensing.165In addition, CNTs were incorporated into PC structures that provided a photonic band gap in the visible light spectrum.166Recently, CNT-based PC structures were investigated for optical applications.167–169Smart materials have been studied extensively and have the potential to be utilized as biosensors due to the unique properties of each material. However, they require further validation using clinical matrices.4.5 MetamaterialsRecently, PC structures based on metamaterials have been investigated for various applications, including imaging and biosensing.169–172For instance, a PC metamaterial with a 3-D woodpile geometry was proposed to excite plasmons with high spectral sensitivity.170The proposed structure was a silver-coated woodpile crystal providing a high surface-to-volume ratio with a sensitivity more than 2600 nm per refractive index unit (RIU) (Fig. 9c and d). In another study, a hyperbolic metamaterial biosensor consisting of 16 alternating layers of thin Al2O3(aluminum oxide) and gold layers was demonstrated to detect biotin (Fig. 9e) with very high sensitivity up to 30 000 nm per RIU.171This 1-D multilayer structure supported guided modes ranging from visible to near infrared, enabled optical biosensing at different spectral regions with ultra-high spectral sensitivity, and detected 10 pM biotin in phosphate buffered saline (Fig. 9f). Light coupling was achieved with a 2-D gold diffraction grating on top of the multilayer films, eliminating the need for additional optical elements (e.g., prism). Although metamaterial-based biosensors enable label-free detection with high sensitivity, they require multiple fabrication steps and may not be compatible with clinically relevant matrices (i.e., whole blood, urine, and saliva).Overall, the integration of PC structures with emerging technologies is promising for biosensing applications at POC owing to compact, flexible, and easy-to-use platforms. In particular, PC-based biosensors composed of smart materials may create a new class of flexible and wearable POC sensors with high sensitivity.5. Multi-target detection capability for PC-based biosensorsPC-based biosensors have been employed to detect multiple biological targets, such as pathogens, proteins, nucleic acids, and glucose, for the diagnosis of a broad range of diseases, including diabetes and cancer. Here, we provide a broad perspective of using PC structures to quantify various molecular interactions ranging from biotin–streptavidin to cancer biomarkers.1735.1 Protein detectionPC structures have been used to capture and detect numerous proteins, such as protein A, Immunoglobulin Gamma (IgG), bovine serum albumin (BSA), and Protein G.157,174,175Streptavidin is often used in conjugation with biotin in experiments to validate the sensitivity and detection limit of new PC geometries due to the extraordinary affinity of streptavidin for biotin.123,176,177PC structures have been employed to investigate the substrate specificity and catalytic activity of certain enzymes, such as acetyl cholinesterase, pepsin and other proteases.103,178In one study, a porous Si-based PC structure was developed to evaluate proteolytic activities of pepsin and subtilisin proteases down to 7 pmol and 0.37 pM, respectively. When coupled with a fluorescence assay, a PC surface can significantly amplify the fluorophore intensity, increase the signal-to-noise ratio and reduce the detection limits. For example, a PC structure was coupled with fluorescence-labeled secondary antibody to detect TNF-α concentrations at pg mL−1levels.185The ability of an assay to detect disease targets at low concentrations at an early stage is very important. In this research, imaging of the PC spots was performed for the multiplex detection of different proteins.Colloidal PC structures have also been widely employed for protein detection. For instance, arranged colloidal nanoparticles embedded inside a hydrogel were used to visually monitor a reflectance shift in response to protein concentration.157In this study, silica nanoparticles were embedded within a poly(ethylene glycol)-diacrylate hydrogel to generate a PC structure. This system was able to observe IgG proteins bound to protein A on the surfaces of the embedded nanoparticles. A color change from orange to green was observed after exposure to 10 mg mL−1IgG, and the detection limit in the color shift was at the concentration of 0.5 mg mL−1IgG (Fig. 10). Since this procedure uses a self-assembly deposition method and does not require advanced manufacturing technology, it is cost-effective; however, the concentrations necessary to observe a visual change are high, and thus, may not be compatible with sensitive detection applications.Fig. 10PC biosensor for capturing and quantification of protein molecules. (a) Colloid PC structure was used to capture IgG proteins. (b) IgG bound to the colloid PC surface and changed the reflected color. (c) Image of the PC surface. A color shift was observed ...By coupling with fluorescence-labeled secondary antibodies, PC-based biosensors have also been utilized to capture allergen-specific immunoglobulin (IgE) antibodies.110,179,180PC structures can enhance fluorescence signals when the optical resonance of the PC surface overlaps with either the excitation or emission spectra of a fluorophore. This enhanced excitation and emission yielded ~7500-fold increase in fluorescence signals.181In a recent study, a PC-enhanced fluorescence (PCEF) microarray platform was used to detect low concentrations of IgE in human sera with a limit of detection of 0.02 kU L−1, which was comparable to current blood-based IgE detection methods.110However, current PC-based allergen platforms rely on fluorescence detection, which limits their use at the POC due to the requirements for labeling, additional instrumentation, and multiple assay preparation steps.5.2 Nucleic acid detectionBiosensing of DNA, RNA, and DNA–protein interactions using PC-based platforms has been studied for various applications, including the determination of infectious agents, identification of genetic disorders,182–185and monitoring of DNA–protein interactions.97,173,186For instance, DNA and protein interactions were evaluated using a 1-D PC slab structure with a TiO2layer over a low index material, and DNA was detected down to nanomolar concentrations.173In this study, a panel of 1000 compounds were screened on a microplate-integrated PC-based biosensing platform (Fig. 11a–c). This platform uses multiple fibers, a motorized stage, and a coupled readout system (SRU Biosystems Bind Reader) capable of recording simultaneous readings from 384-wells. This platform has significant potential for drug-screening studies at the POC in resource-constrained settings since it incorporates a disposable and inexpensive 384-well microplate. The platform can further be utilized for the detection of RNA–protein and protein–protein interactions, and may shed light on gene expression at the cellular and molecular levels.187In addition to 1-D PC slab structures, colloid PCs have also been utilized for nucleic acid detection. In this study, self-assembled polystyrene beads were utilized to fabricate a colloidal PC structure that could detect hybridized DNA down to 13.5 fM.188In another study, a planar waveguide was employed for the detection of single-stranded DNA at a concentration of 19.8 nM.98The use of PC structures is a promising alternative to the conventional polymerase chain reaction (PCR) techniques for nucleic acid detection due to their low cost, ease-of-use, rapid response, and high detection capacities.Fig. 11Monitoring DNA–protein interaction using a PC biosensor. (a) Image of a 384-well plate integrated with a PC platform for drug screening. (b) Drug screening for protein–DNA binding inhibition. An outstanding molecule was recorded using ...5.3 Applications in cancerBiosensors are widely employed in the detection of biomarkers for diagnosis and prognosis of cancer. Currently, various bio-markers, such as epidermal growth factor receptor (EGFR), human epidermal growth factor receptor 2 (HER2), prostate-specific antigen (PSA), carcinoembryonic antigen (CEA), tumor necrosis factor-α (TNF-α), and calreticulin (CRT), are under clinical study for diagnosis of cancer.189–191Detecting these biomarkers at an early stage of malignancy can contribute to better treatment outcomes and significantly increase the quality of life for cancer patients.Recently, PC-based biosensors have been employed in diagnosis and early detection of cancer.189,192,193In one study, a waveguide integrated with a cavity was employed for the detection of CEA protein for the diagnosis of colon cancer (Fig. 11d–f).192This platform provided a detection limit for CEA protein down to the 0.1 pg mL−1level. In another study, a cavity and a line defect were fabricated on the surface of a silicon substrate to capture lung cancer cells.189In another study, 1-D PC slabs obtained from quartz materials were fabricated via NIL. This PC-based platform was used to detect 21 different cancer biomarkers, including HER2, EGFR, and prostate-specific antigen (PSA) with a detection range from 2.1 pg mL−1to 41 pg mL−1.193This multiplexed cancer biomarker platform can function in both fluorescence and non-fluorescence modes, providing flexibility to work with labelled and non-labelled biotarget sensing.5.4 Pathogen detectionRapid identification and quantification of pathogens, such as bacteria and viruses, is important for diagnosis and prognosis in the POC environments at resource-constrained settings. Recently, PC structures have been deployed at the POC for diagnoses of infectious diseases caused by pathogenic agents and toxins.92,109,194For instance, 2-D PC pillars, fabricated on polymer substrates using NIL, were used for the detection of human influenza virus (H1N1) in human saliva. This platform can detect H1N1 antigens at a concentration as low as 1 ng mL−1.93In another study, polymer-2-D pillar PC structures were used to detect L. pneumophila bacteria down to 200 cells per mL.96PC-based platforms can also be used for the detection of viruses such as rotavirus, HIV-1, and human papilloma virus-like particles.92,94,195To detect HIV-1, a PC surface was functionalized with anti-gp120 antibody for capturing HIV-1 ranging from 104copies per mL to 108copies per mL (Fig. 11g–i). In another study, silica microspheres were used to fabricate colloidal PC structures for the detection of multiple mycotoxins in cereal samples.201Although microspheres are fabricated inexpensively as droplets in water–oil two-phase flow, this system still depends on fluorescence measurements and may be subject to undesirable background variation due to the inherent labelling procedure.1965.5 Glucose sensingDetection of glucose holds significant importance in POC diagnostics for diabetics.197,198Although glucose sensors are globally available as POC tools, there is still a need for non-invasive glucose biosensing using new and advanced technology sensing platforms, including PC-based biosensors.199,200Non-invasive monitoring can be achieved by collecting samples other than blood such as sweat, tear fluid, and urine. For instance, a hybrid photonic structure (1-D Bragg gratings) was fabricated from silver nanoparticles and a hydrogel to detect glucose, fructose, and lactate. This platform was tested with urine samples from diabetes patients with a detection limit of 90 μM.41In another study, the poly(hydroxyethyl methacrylate)-based (pHEMA) matrix was UV cross-linked, and silver nanoparticles were dispersed in this hydrogel. A pulse laser was then used to align the silver particles in confined regions creating a periodic structure, which ultimately provided PC properties.201Furthermore, the platform was also tested in artificial tear fluid for accurate glucose sensing (Fig. 12). This platform is unique because it employs inexpensive hydrogels and can be linked to biomolecules by easy conjugation with carboxylic groups. In this study, PC structures were fabricated from polystyrene colloidal spheres integrated with hydrogel for glucose sensing at 50 μM.Fig. 12Glucose sensing from urine using a PC biosensor. (a) Scheme of Ag incorporated hydrogel PC structure. (b) Simulation of a PWS as a result of the pH change. (c) The PWS at varying pH values and its corresponding observable color code. Reproduced from ref. ...Overall, although PC-based platforms have been employed for the detection of glucose with encouraging results, their widespread utilization for glucose sensing and diabetes diagnosis needs to be evaluated for reliable and accurate sensing.6. Surface chemistry approaches in PC-based biosensing applicationsPC-based biosensing platforms consist of an optically active layer and immobilized binder molecules, such as affibodies, nanobodies, peptides, antibodies, and antibody fragments to ensure biotarget capture.157,158,202Depending on the material type used for the optically active layer, binder molecules can be immobilized using various functionalization strategies, including physical adsorption (physisorption), covalent binding, and affinity-assisted coupling. Furthermore, anti-fouling agents play an important role in reducing the non-specific interactions and improving the sensitivity and specificity. In this section, we discuss surface chemistry approaches for TiO2-, Si-, and SiO2- based PC sensors, as well as anti-fouling agents to minimize non-specific binding.Physical adsorption strategies are used to accumulate bio-targets onto optically active layers via hydrogen bonds and van der Waals interactions. By applying plasma techniques, the net charge on a surface can be changed to increase the surface coverage of a biotarget.203For instance, PC waveguide structures with a Si layer were employed to monitor the physisorption of bovine serum albumin (BSA).35In this study, a BSA solution was directly applied to the PC waveguide surface and non-specific physical adsorption of BSA molecules was monitored. Although physisorption is simple, easy-to-apply, and does not require any wet-chemistry or laborious modification steps, it can interfere with other biomolecules in the detection buffer. Furthermore, physisorption is based on weak interactions between the surface and the biotarget, and is therefore not stable and can easily detach when surface charge is altered by changes in pH, ionic content, and temperature.Covalent binding is one of the standard methods for immobilization approaches using the strong chemical linkage that forms between a sensor surface and binder molecules. TiO2and SiO2surfaces are common substrates for optical sensors; however, performing coupling on these surfaces is laborious since it requires layer-by-layer surface functionalization including surface activation, functional group generation, and binder immobilization. Silane-based molecules with a variety of functional groups are commonly used to immobilize biomolecules onto glass surfaces. A standard protocol for silanizing a surface begins with cleaning the surface using a strong oxidizing agent, such as piranha solution (a mixture of H2O2and H2SO4) to increase the density of silanol groups exposed on a surface, which also increases the hydrophilicity of the sensor surface. Then, a silanization agent, such as (3-aminopropyl)triethoxysilane (APTES) or (3-aminopropyl)trimethoxysilane–tetramethoxysilane (MPTMS or 3-MPS), is applied to generate a self-assembled monolayer (SAM), which consists of hydroxyl groups, alkyl backbone chains, and functional tail groups.204,205Alkyl chains enable the height of captured biotargets to be adjusted from the sensor surface, and can also contain active tail groups, such as amine, carboxyl, and succinimide esters to tether binder molecules (Fig. 13).Fig. 13Surface chemistry approaches for PC-based biosensors. Initially, the PC surface (i.e., TiO2) is treated with piranha solution and/or oxygen plasma to increase the hydrophilicity by exposing polar molecules on the surface. The surface is then immersed ...The latter surface functionalization approach provides affinity-based interactions at specific regions on binders and anchor molecules.206However, clinical samples have a complex composition including proteins, lipids, and sugar units that can non-specifically adhere to a sensor surface. Non-specific binding can occur at active, passivated, and untreated areas on the sensor. Anti-fouling agents, including chemical modifiers, proteins, and polymeric substances, serve to prevent non-specific binding and increase the detection accuracy of target molecules. Furthermore, working with biospecimens requires sample preparation steps to avoid signal fluctuations and inaccuracies, considerably increasing the complexity of biosensing assays.207,2087. Current challenges and limitations for biosensors at the POCIn this section, we discuss a number of emerging technologies with respect to challenges associated with current biosensors at the POC. These criteria include label-free sensing, assay complexity, assay time, multi-target detection, read-out mechanisms, fabrication methods, and applicability for clinical testing. We compare PC-based biosensing platforms with up-to-date bio-sensing technologies: nanomechanical sensors, plasmonics tools, electrical sensing platforms, and magnetosensors (Table 2).7.1 Label-free biosensingLabeling of biotargets, often with fluorescence molecules, has been extensively utilized in biosensing applications to enhance signal readout for improving measurements. However, introducing a label potentially adds complexity, increases experimental errors, and presents additional inefficiencies and uncertainties, such as quenching effects and photobleaching.209Additionally, labeling a biomolecule can significantly alter its characteristic properties (conformation, solubility, and affinity).210Considering the challenges associated with labeling, label-free assays can reduce cost, complexity, and time for POC tests by eliminating the use of labels, dyes, and high-volume of reagents.211–213Therefore, there is a demand for label-free, rapid, sensitive and accurate bio-sensing platforms at the POC, which will address the challenges associated with current label-based biosensor strategies. In this regard, PC structures represent a new class of biosensors that hold promise for label-free biosensing with potential applications at the POC.7.2 Assay timeTo be sustainable, emerging technologies need to provide rapid, inexpensive, and multiplexed solutions over existing assays and methods. Some platforms require filtration-type sample preparation steps to concentrate targets in the sample, which also increases assay complexity and time.214From a POC perspective, biosensing platforms need to be fabricated with inexpensive materials and methods using simple and inexpensive production techniques. For instance, some of the biosensing platforms require clean room facilities and multiple chemical etches for their fabrication, which may significantly increase the total assay cost.214The read-out mechanism is another pivotal criterion to obtain reliable measurements at the POC. For instance, nano-mechanical platforms, including quartz crystal microbalance and piezoelectric sensors, are affected by multiple external parameters such as temperature and vibration and require additional equipment (e.g., vibration insulation and temperature control systems) to minimize these external interferences to ensure reliable measurements.215This additional equipment limits the portability and may also increase the cost, thus not satisfying some of the key requirements for a POC device.7.3 Multiplexing capabilityAn ideal biosensing platform needs to detect multiple targets. This feature will provide a wide window to evaluate different targets on a single platform, increasing its applicability for versatile POC testing. To immobilize various antibodies/binders onto a single sensor surface, PC-based biosensor platforms can benefit from antibody printing technologies (Table 2).1937.4 Clinical validationBiological specimens, such as blood, saliva, urine, and sweat, have distinct characteristics. These matrices have various ionic content, ionic strength, pH, and a diverse makeup comprised of cells, proteins, and lipids. Detecting biotargets in biological matrices constitutes one of the major challenges for biosensing. For instance, electrical-based sensing platforms measure electrical potential via different modalities, such as amperometry, potentiometry, and capacitance read-outs. Most of these platforms require replacing the biological matrix with non-ionic fluids, and therefore multi-step flow or centrifugation is required to minimize or eliminate interfering factors for read-out.115,216Ultimately, biosensors need to undergo extensive clinical validation before they can be used at the POC.8. Future outlook for PC-based biosensors at POC diagnosticsThe global biosensor market is valued at approximately US$ 13 billion in 2013 and projected to grow substantially to US$ 22 billion by 2020.217On-site (bedside) biosensors at the POC are poised to transform the healthcare industry as invaluable tools for the diagnosis and monitoring of diseases, infections, and pandemics worldwide. Advances in flexible, wearable, and implantable sensing technologies integrated with responsive materials can potentially connect patients to the clinic, thus providing continuous monitoring, such as glucose sensing for the patients with diabetes at the point-of-need.218,219Due to their characteristics including flexibility (e.g., hydrogels) and integration capability with smart materials (e.g., CNTs and graphene), PC-based sensors will be an asset to the current wearable continuous monitoring tools and sensors.A color shift that can be observed with the naked eye or with the help of a color legend is valuable at the POC. One interesting potential application for PC-based structures is to dynamically change the optical properties in response to environmental parameters, such as geometry, pH, and temperature. An example can be found in nature as suggested by a recent study on chameleon skin, which revealed the presence of guanine pillar-like nanocrystal PC structures.220When relaxed, crystals were randomly distributed, but changed to a square or hexagonally-packed lattice geometry when excited, thereby changing the skin’s visible colors (Fig. 14). Inspired by this example, PC structures could also be fabricated as simple diagnostic tools to produce a color shift against an external stimulus with a subsequent change in geometry. This method may potentially eliminate the need for large and expensive optical devices for biosensors in the POC applications.Fig. 14Spatial arrangements of PC structures in chameleon’s body. (a) The color change of two male chameleons. The left column indicates the relaxed state; the right column indicates the excited state. (b) TEM images of these two states. In the relaxed ...PC structures with more complicated geometries, such as 2-D PCs, are sensitive to changes in the refractive index in nano-and micro-scale volumes. Large wavelength shifts were experimentally observed after binding single sub-micron sized metallic and polymeric nanoparticles.122,221–224Detection of virus particles using these structures are highly promising, since viruses strongly interact with light, and can be easily captured on top of or inside photonic crystals.34,194However, biological detection of viral particles using 2-D PC structures has been difficult due to the low refractive index contrast between water and biological targets. Recent work with human papillomavirus-like particles spiked into serum has suggested that the detection of biologically relevant particles is possible, with a detection limit in the nanomolar range.929. ConclusionDetection of biomolecules at the POC faces multiple challenges, including the lack of centralized labs, limited technical capabilities, the absence of skilled staff, and poor health care management systems (particularly in resource-limited settings). PC-based biosensors represent a novel class of advanced optical biosensors that readily address these drawbacks. PC structures are used as biosensors for cells, bacteria, viruses, and numerous biomolecules, such as proteins, cancer biomarkers, allergens, DNAs, RNAs, glucose, and toxins. These structures can be manufactured with metals, oxides, plastics, polymers, and glass in mass quantities using NIL technology or wet chemical synthesis of colloidal and polymer structures. Recently, PC structures have been integrated with emerging technologies such as smart-phones, flexible materials, and wearable sensors to enhance their utilization as potential diagnostic tools at the POC. However, clinical specimens may require sample preparation steps such as filtration, which may limit the use of PC-based biosensors at the POC. Additionally, complex biological fluids comprising cells and tissues may interfere with the transducer of biosensors and some of the delicate PC structures might experience challenges with the sensing mechanism including read-out systems. In addition, PC structures have been translated to a few products in biosensing, chemical and humidity sensing. PC-based biosensors represent a new class of advanced technology products that can be good candidates for a wide array of applications at the POC.AcknowledgmentsU. D. is a founder of and has an equity interest in: (i) DxNow Inc., a company that is developing microfluidic and imaging technologies for point-of-care diagnostic solutions, and (ii) Koek Biotech, a company that is developing microfluidic in vitrofertilization (IVF) technologies for clinical solutions. U. D.’s interests were viewed and managed in accordance with the conflict of interest policies. U. D. would like to acknowledge National Institutes of Health (NIH) R01 A1093282, R01 GM108584, R01 DE02497101, NIH R01 AI120683.BiographiesHakan InanHakan Inan is a postdoctoral research fellow at the Canary Cancer Early Detection Center at the Medicine Faculty, Stanford University. He is working on microfluidics and nanotechnology-based diagnostic devices and techniques for cancer diagnosis and prognosis for point-of-care applications. He obtained his Master and PhD degrees in nanotechnology. He joined Professor Utkan Demirci’s lab at Stanford University in 2014 as a visiting graduate student and has performed his research in the same group since then. He has 12 years of teaching experience at high school and undergraduate level, where he taught chemistry and biochemistry.Muhammet PoyrazMuhammet Poyraz is a PhD student in electrical engineering at Stanford University and a graduate researcher at the Canary Center at Stanford for Cancer Early Detection. He received his BS degree from Bilkent University, Turkey, in electrical and electronics engineering. He joined Professor Utkan Demirci’s lab at Stanford University in 2016 as a graduate student. He is currently working on photonic crystal and plasmonic based biosensing technologies for point-of-care applications.Fatih InciFatih Inci received the PhD degree from Istanbul Technical University (Turkey), focusing on biosensor design and development for clinical and pharmaceutical applications. He was then appointed as a Postdoctoral Research Fellow at Harvard Medical School and Stanford University School of Medicine. Dr Inci is currently working as a Basic Life Science Research Scientist at Stanford University School of Medicine, Canary Center at Stanford for Cancer Early Detection. His research is focused on creating point-of-care diagnostic technologies, lab-on-a-chip platforms, nanoplasmonic biosensors, and surface chemistry approaches for medical diagnostics. Dr Inci’s work has been highlighted in the NIH–NIBIB, Boston University, Canary Center at Stanford, Johns Hopkins University, JAMA, Nature Medicine, AIP, Newsweek, and Popular Science.Mark A. LifsonMark Lifson is a biomedical and computer engineer currently working as a postdoctoral research fellow at Stanford. He obtained his Bachelor of Science in computer engineering from the Rochester Institute of Technology, and his Master of Science and Doctorate from the University of Rochester in biomedical engineering. His research interests include developing ultra-sensitive sensors for biomarker detection. He has expertise in photonic crystals, microfluidics, localized surface plasmon resonance, and smart colloidal nanoparticles.Brian T. CunninghamBrian T. Cunningham is the Willett Professor of Engineering in the Department of Electrical and Computer Engineering at the University of Illinois at Urbana-Champaign, where he also serves as the Director of the Micro and Nanotechnology Laboratory. His research interests include the development of biosensors and detection instruments for pharmaceutical high throughput screening, disease diagnostics, point-of-care testing, life science research, and environmental monitoring. He has published 160 peer-reviewed journal articles, and is an inventor on 83 patents. Prof. Cunningham was a co-founder of SRU Biosystems in 2000, and founded Exalt Diagnostics in 2012 to commercialize photonic crystal enhanced fluorescence technology for disease biomarker detection. Acoustic MEMS biosensor technology that he developed at the Draper Laboratory has been commercialized by Bioscale, Inc. Prof. Cunningham’s work was recognized with the IEEE Sensors Council Technical Achievement Award and the IEEE Engineering in Medicine and Biology Technical Achievement Award. He is a member of the National Academy of Inventors and a Fellow of IEEE, OSA, and AIMBE.Utkan DemirciUtkan Demirci is an Associate Professor at the School of Medicine, Department of Radiology, Canary Center at Stanford for Cancer Early Detection. His research interests involve the applications of microfluidics, nanoscale technologies and acoustics in medicine, especially portable, inexpensive, disposable technology platforms in resource-constrained settings for global health problems and 3-D biofabrication and tissue models including 3-D cancer and neural cultures. Dr Demirci has published over 120 peer-reviewed publications, over 150 conference abstracts and proceedings, 10 book chapters, and edited four books. His work has been recognized by numerous awards including the NSF Faculty Early Career Development (CAREER) Award and the IEEE-EMBS Early Career Achievement Award. He was selected as one of the world’s top 35 young innovators under the age of 35 (TR-35) by the MIT Technology Review. His patents have been translated into start-up companies including DxNOW and Koek Biotech. Some of these technologies are clinically available across the globe.